6533b824fe1ef96bd1280ca2

RESEARCH PRODUCT

Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

Jacqueline C.m. WittemanNicole Probst-henschNicole Probst-henschGail DaviesAnna KöttgenAnna KöttgenQunyuan ZhangQunyuan ZhangPio D'adamoNicholas G. MartinSilvia ToreStephan J. L. BakkerGian Andri ThunGian Andri ThunCinzia SalaPeter P. PramstallerTamara B. HarrisAaron IsaacsSheila UliviRossella SoriceXuan LiuAndrew A. HicksHenry VölzkeDaniela RuggieroArnold Von EckardsteinYukinori OkadaAndres MetspaluJeffrey MetterSerena SannaJennifer E. HuffmanPhilipp S. WildFlorian ErnstEva AlbrechtMary F. FeitosaClaudia SchurmannKathrin BuddeVeikko SalomaaDarina CzamaraElizabeth G. HollidayMarcel BruinenbergLaura PortasMaris LaanAlan J. GowCaroline HaywardTim D. SpectorOzren PolasekIlja M. NolteRodney J. ScottMassimo ManginoDavid S. SiscovickNilesh J. SamaniNilesh J. SamaniToomas HallerLaura FrogheriA. JulaMika KähönenBruce H. R. WolffenbuttelCaroline S. FoxCaroline S. FoxDavid R. JacobsJulia ShiYusuke NakamuraDaniel I. ChasmanFabian J. TheisAlan F. WrightAyse DemirkanFrancesco CuccaPaolo GaspariniPaul M. RidkerOlli T. RaitakariDaniela TonioloMaristella SteriMario PirastuSusan CampbellMaksim StruchalinSo-youn ShinMark J. CaulfieldH.-erich WichmannGrant W. MontgomeryÅSa JohanssonAlexander TeumerUlf GyllenstenRobert M. PlengeRobert M. PlengeMichel BurnierMichael SchallertJan KrumsiekJing Hua ZhaoAndres SalumetsPoorva MudgalPoorva MudgalAnke TönjesJames F. MeschiaGauti Kjartan GislasonPerttu SaloAngela DöringAfshin ParsaVilmundur GudnasonPatrick F. McardleRita P. S. MiddelbergW. H. Linda KaoAldi KrajaChristopher OldmeadowAdrienne TinLoic YengoMurielle BochudGerjan NavisChristian GiegerToshiko TanakaCornelia M. Van DuijnSamuli RipattiSamuli RipattiSamuli RipattiTerho LehtimäkiClaudia LangenbergBernhard O. BoehmConall M. O'seaghdhaConall M. O'seaghdhaEric BoerwinkleNicole SoranzoTõnu EskoSusan M. FarringtonMike A. NallsJohn F. PedenHyon K. ChoiHyon K. ChoiAnuj GoelAndrew D. JohnsonNorman KloppAnne GrotevendtHalit OngenMarcus E. KleberMyriam FornageMalcolm G. DunlopIgor RudanIgor RudanFederico MurgiaBeverley BalkauJorma ViikariChristopher P. NelsonChristopher P. NelsonGérard WaeberLenore J. LaunerIvana PersicoInga ProkopenkoGuo LiTatijana ZemunikElisabetta TrabettiTanja ZellerHugh WatkinsQiong YangQiong YangJames F. WilsonPeter VollenweiderVeronique VitartMarkus PerolaMarkus PerolaMarkus PerolaNicola PirastuOlivier DevuystIrene Mateo LeachJohn AttiaBruce M. PsatyBruce M. PsatyNicholas J. WarehamSusanne LucaeJosef CoreshIngrid B. BoreckiClaudia HundertmarkWeihua ZhangWeihua ZhangLuigi FerrucciJaspal S. KoonerJaspal S. KoonerStefan KloiberLynda M. RoseNaoyuki KamataniZoltán KutalikZoltán KutalikGiovanni MalerbaIan J. DearyAlbert V. SmithHelena SchmidtEva LattkaPhilippe FroguelHarry CampbellMedea ImbodenMedea ImbodenAntonio LupoAngelo L. GaffoVasiliki LagouAlan R. ShuldinerJohn WhitfieldAbbas DehghanWinfried MärzWinfried MärzElin OrgAlbert HofmanMargus ViigimaaKonstantin StrauchToshihiro TanakaAndrew B. SingletonStefania BandinelliChristian HengstenbergXinzhong LiWiek H. Van GilstPim Van Der HarstGiorgio PistisJerome I. RotterMaria Grazia PirasGary C. CurhanBrenda W.j.h. PenninxBrenda W.j.h. PenninxBrenda W.j.h. PenninxRamaiah NagarajaNabila Bouatia-najiChristian MüllerRonald P. StolkPau NavarroLorna M. LopezRuth J. F. LoosAlbert TenesaJohannes H. SmitPeter KraftGiovanni GambaroSarah H. WildPatricia B. MunroeAndré G. UitterlindenIvana KolcicBernhard R. WinkelmannPankaj SharmaJohn C. ChambersJohn C. ChambersNicholas D. HastieMatthias NauckHarold SniederMichael StumvollReinhold SchmidtHans L. HillegeKiang LiuFernando RivadeneiraOwen M. WoodwardMorris J. BrownMargus PutkuSabine SchipfMirna KirinKay-tee KhawMelanie WaldenbergerEvropi TheodoratouMarina CiulloMichiaki Kubo

subject

Candidate geneInhibins/geneticsGenome-wide association studyGENETIC-LOCIchemistry.chemical_compound0302 clinical medicineserum urateGene FrequencyGout/bloodassociation analysis serum urateGlucose/metabolismSettore MED/14 - NEFROLOGIAHyperuricemiaserum; urate; genePOPULATIONMETABOLIC SYNDROMEGenetics0303 health scienceseducation.field_of_studybiologyPolymorphism Single Nucleotide/genetics3. Good healthHYPERURICEMIAGenetic Loci/genetics/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingSLC22A12Single Nucleotide/geneticsSNPsSignal TransductionMOLECULAR PHYSIOLOGYserum urate concentrations gout genome-wide meta-analysisEuropean Continental Ancestry GroupPopulationPolymorphism Single NucleotideWhite PeopleUric Acid/bloodserum urate concentrationsgenome-wide meta-analysis03 medical and health sciencesSDG 3 - Good Health and Well-beinguric acidGeneticsmedicineHumansInhibinsPolymorphismeducation030304 developmental biology030203 arthritis & rheumatologyAnalysis of VarianceGOUTIDENTIFICATIONTRANSPORTERCARDIOVASCULAR-DISEASE RISKta3121medicine.diseaseassociation analysisGoutmeta-analysisGlucosechemistryGenetic Locigenome-wide association studiesbiology.proteinSignal Transduction/geneticsUric acidURIC-ACID LEVELSGenome-Wide Association StudySLC2A9

description

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout. © 2013 Nature America, Inc. All rights reserved.

yearjournalcountryeditionlanguage
2013-02-01
10.1038/ng.2500https://www.bib.irb.hr/639277